Paediatric obesity and metabolic syndrome associations with cognition and the brain in youth: Current evidence and future directions.

Obesity and components of the metabolic syndrome (MetS) are associated with differences in brain structure and function and in general and food-related cognition in adults. Here, we review evidence for similar phenomena in children and adolescents, with a focus on the implications of extant research for possible underlying mechanisms and potential interventions for obesity and MetS in youth. Current evidence is limited by a relative reliance on small cross-sectional studies. However, we find that youth with obesity and MetS or MetS components show differences in brain structure, including alterations in grey matter volume and cortical thickness across brain regions subserving reward, cognitive control and other functions, as well as in white matter integrity and volume. Children with obesity and MetS components also show some evidence for hyperresponsivity of food reward regions and hyporesponsivity of cognitive control circuits during food-related tasks, altered brain responses to food tastes, and altered resting-state connectivity including between cognitive control and reward processing networks. Potential mechanisms for these findings include neuroinflammation, impaired vascular reactivity, and effects of diet and obesity on myelination and dopamine function. Future observational research using longitudinal measures, improved sampling strategies and study designs, and rigorous statistical methods, promises to further illuminate dynamic relationships and causal mechanisms. Intervention studies targeted at modifiable biological and behavioural factors associated with paediatric obesity and MetS can further inform mechanisms, as well as test whether brain and behaviour can be altered for beneficial outcomes.

The relationship between weight loss and cognitive function in bariatric surgery.

BACKGROUND: Previously, we reported short-term improvements in auditory attention, oromotor processing speed, and executive function during the active weight loss phase following bariatric surgery that persisted out to 3 months. In this study, our aims were to investigate the relationship between weight loss and cognitive performance in these patients 1 year following vertical sleeve gastrectomy (VSG) and Roux-en Y gastric bypass (RYGB) surgery and to determine whether preoperative cognitive performance predicted weight loss. METHODS: Adult women ages 18-55 approved for bariatric surgery completed a cognitive battery prior to and at 2, 12, 24, and 52 weeks following VSG (N = 17) or RYGB (N = 18). Scores from each task were assigned to one of the following cognitive domains: auditory attention, processing speed, memory, and executive functioning. Weight loss and cognitive scores for each domain were calculated and compared between cohorts. RESULTS: RYGB surgery resulted in greater weight loss at 1-year follow-up relative to VSG. Both VSG and RYGB procedures resulted in improved performance on different measures of auditory attention and both surgery groups improved across all processing speed tasks. Within the executive function domain, both groups showed improvements, but only the RYGB procedure resulted in improved performance in the Trail Making Test. Baseline auditory attention and memory performance predicted weight loss at 1 year following RYGB but not VSG surgery. Controlling for baseline cognitive performance, percent total weight loss predicted auditory attention at 1 year following RYGB but not VSG surgery. CONCLUSIONS: Bariatric surgery type may result in selective improvements in cognition during the first year following surgery. Presurgical cognitive performance as well as surgery type appears to influence weight loss outcomes.

Investigating relationships between post-prandial gut hormone responses and taste liking ratings prior to and following bariatric surgery: a pilot study.

BACKGROUND: Alterations in gut hormone secretion and reported changes in taste preferences have been suggested to contribute to the weight-reducing effects of bariatric surgery. However, a link between changes in gut hormone secretion and taste preferences following bariatric surgery has yet to be elucidated. METHODS: Here we examined the potential relationships between gut hormone responses (GLP-1 and PYY3-36 peak, ghrelin trough) to a test meal of Ensure and liking ratings for taste mixtures varying in sugar and fat content before and following bariatric surgery (vertical sleeve gastrectomy (VSG): N = 4; Roux-en Y gastric bypass (RYGB): N = 8). RESULTS: Significant increases in GLP-1 and PYY3-36 peak and a significant drop in ghrelin trough were observed following surgery. Pre- and postoperation, patients with higher postprandial GLP-1 or PYY3-36 peaks gave lower liking ratings for mixtures containing a combination of fat and sugar (half and half + 20% added sugar) whereas, for the combined surgery analyses, no relationships were found with solutions comprised of high fat (half and half + 0% sugar), predominantly high sugar (skim milk + 20% added sugar), or low fat and low sugar (skim milk + 0% added sugar). Within the RYGB patients, patients with the greatest increase in postprandial GLP-1 peak from preoperation to postoperation also demonstrated the greatest decrease in liking for half & half + 20% added sugar and skim milk + 20% added sugar, but not the unsweetened version of each solution. No pre- or postoperative relationship between ghrelin and liking ratings were observed. CONCLUSION: Gut hormone responses following bariatric surgery may contribute to taste processing of sugar+fat mixtures and together influence weight loss.

One Year Follow-Up of Taste-Related Reward Associations with Weight Loss Suggests a Critical Time to Mitigate Weight Regain Following Bariatric Surgery.

BACKGROUND: Weight regain is a concerning issue in bariatric patients. We previously demonstrated that taste-related reward processing was associated with six-month weight loss outcomes following Roux-en-Y gastric bypass (RYGB) but not vertical sleeve gastrectomy (VSG). Here, we assessed whether these taste factors persisted in predicting weight loss, and weight regain, at one year post-surgery. METHODS: Adult women enrolled in a longitudinal study of taste preferences following bariatric surgery completed behavioral and neuroimaging assessments at one year post-surgery. RESULTS: RYGB produced better weight loss relative to VSG, with weight regain and greater weight loss variability observed from six months to one year post-VSG. Changes in liking for high fat at 2 weeks post-surgery from baseline remained a predictor of weight loss in RYGB, but other predictors did not persist. Average liking ratings rebounded to baseline and higher self-reported food cravings and dietary disinhibition correlated with poorer weight loss at one year post-surgery. CONCLUSION: Initial anatomical and metabolic changes resulting from RYGB that reset neural processing of reward stimuli in the mesolimbic pathway appear to be temporary and may be contingent upon post-operative eating behaviors returning to preoperative obesogenic tendencies. Six months post-surgery may be a critical window for implementing interventions to mitigate weight gain.

Binge Watching during COVID-19: Associations with Stress and Body Weight.

Binge watching is becoming increasingly common and may impact energy balance and body weight. The COVID-19 pandemic has created conditions conducive to binge watching and increased stress. We investigated relationships between COVID-related stress and binge watching behaviors, and potential variation in this relationship by body weight. Adults (n = 466) completed a cross-sectional online survey assessing binge watching behaviors during and before the pandemic, COVID-related stress, and body weight. Participants reported an increase in binge watching frequency from before to during the pandemic (F1,401 = 99.970, p < 0.001), with rates of high binge watching ("3-4 times per week" to "3 or more times per day") increasing from 14.6% to 33.0%. Binge watching episode duration increased from 3.26 ± 1.89 h to 3.92 ± 2.08 h (p < 0.001). The increase in binge watching frequency was greatest in individuals with obesity and high stress (F 4,401 = 4.098, p = 0.003). Participants reporting high stress reported higher frequency of eating while binge watching, as well as higher levels of negative emotional triggers, consequences to binge watching, and lack of control over binge watching (all p < 0.001). Our results show that binge watching increased during the pandemic, with greater increases among individuals reporting higher COVID-related stress, especially those with obesity, and concomitant effects on eating, and highlight a need for interventions to minimize the obesogenic impact of binge watching during the pandemic.

Gastrointestinal peptides in eating-related disorders.

Food intake is tightly controlled by homeostatic signals sensitive to metabolic need for the regulation of body weight. This review focuses on the peripherally-secreted gastrointestinal peptides (i.e., ghrelin, cholecystokinin, glucagon-like peptide 1, and peptide tyrosine tyrosine) that contribute to the control of appetite and discusses how these peptides or the signals arising from their release are disrupted in eating-related disorders across the weight spectrum, namely anorexia nervosa, bulimia nervosa, and obesity, and whether they are normalized following weight restoration or weight loss treatment. Further, the role of gut peptides in the pathogenesis and treatment response in human weight conditions as identified by rodent models are discussed. Lastly, we review the incretin- and hormone-based pharmacotherapies available for the treatment of obesity and eating-related disorders.

COVID-19 Stress and Food Intake: Protective and Risk Factors for Stress-Related Palatable Food Intake in U.S. Adults.

(1) Background: The coronavirus (COVID-19) pandemic has caused disruptions to what people eat, but the pandemic's impact on diet varies between individuals. The goal of our study was to test whether pandemic-related stress was associated with food intake, and whether relationships between stress and intake were modified by appetitive and cognitive traits. (2) Methods: We cross-sectionally surveyed 428 adults to examine current intake frequency of various food types (sweets/desserts, savory snacks, fast food, fruits, and vegetables), changes to food intake during the pandemic, emotional overeating (EOE), cognitive flexibility (CF), and COVID-19-related stress. Models tested associations of stress, EOE, and CF with food intake frequency and changes to intake. (3) Results: Models demonstrated that the positive relationship between stress and intake of sweets/desserts was stronger with higher EOE, while the positive relationship between stress and intake of chips/savory snacks was weaker with higher CF. Higher EOE was associated with greater risk of increased intake of palatable foods. (4) Conclusions: Findings suggest that emotional overeating may escalate stress-associated intake of high-sugar foods, and cognitive flexibility may attenuate stress-associated intake of high-fat foods. Differences in appetitive and cognitive traits may explain changes to and variability in food intake during COVID-19, and efforts to decrease emotional overeating and encourage cognitive flexibility could help lessen the effect of COVID-19-related stress on energy dense food intake.

The influence of COVID-19-related stress on food motivation.

The COVID-19 pandemic and public health measures to reduce its transmission have increased stress. Stress is associated with alterations in eating behavior which may be partly driven by effects on food-related motivation. To investigate effects of COVID-related stress on food motivation, we recruited adults (N = 429; 272 F, 157 M) to complete an online survey via Amazon MTurk in May 2020. Current COVID-related stress, retrospective pre-COVID stress, and motivation in relation to individualized preferred foods from five categories (sweet snacks, fruit, savory snacks, vegetables, and fast food) were assessed. Food motivation measures included willingness to wait, willingness to expend low effort [finger taps], willingness to expend high effort [jumping jacks], and willingness to pay for hypothetical delivery of the food item. Food motivation for each food type was assessed using a novel instrument designed for brief assessment of multiple aspects of food motivation across multiple food types. Participants were willing to pay the most for fast food followed by sweet snacks, and willing to wait longer for sweet snacks relative to other food types. While fast food and sweets also generated the most willingness to expend high and low effort, willingness to expend low effort for fruit was similar to that for fast food and sweets, and willingness to expend high effort for fruit was comparable to that for fast food. Participants were least willing to pay or expend low effort for vegetables. Higher COVID-related stress levels were associated with willingness to expend more effort and pay more for food items. These data collected during the pandemic demonstrate that highly processed and sweet foods have high motivating value across multiple measures of motivation, and COVID-related stress increases food motivation across food categories. Interventions to mitigate stress and target the link between stress and overeating may help to limit the effects of the COVID-19 pandemic on obesity.

Phase-locking of resting-state brain networks with the gastric basal electrical rhythm.

A network of myenteric interstitial cells of Cajal in the corpus of the stomach serves as its "pacemaker", continuously generating a ca 0.05 Hz electrical slow wave, which is transmitted to the brain chiefly by vagal afferents. A recent study combining resting-state functional MRI (rsfMRI) with concurrent surface electrogastrography (EGG), with cutaneous electrodes placed on the epigastrium, found 12 brain regions with activity that was significantly phase-locked with this gastric basal electrical rhythm. Therefore, we asked whether fluctuations in brain resting state networks (RSNs), estimated using a spatial independent component analysis (ICA) approach, might be synchronized with the stomach. In the present study, in order to determine whether any RSNs are phase-locked with the gastric rhythm, an individual participant underwent 22 scanning sessions; in each, two 15-minute runs of concurrent EGG and rsfMRI data were acquired. EGG data from three sessions had weak gastric signals and were excluded; the other 19 sessions yielded a total of 9.5 hours of data. The rsfMRI data were analyzed using group ICA; RSN time courses were estimated; for each run, the phase-locking value (PLV) was computed between each RSN and the gastric signal. To assess statistical significance, PLVs from all pairs of "mismatched" data (EGG and rsfMRI data acquired on different days) were used as surrogate data to generate a null distribution for each RSN. Of a total of 18 RSNs, three were found to be significantly phase-locked with the basal gastric rhythm, namely, a cerebellar network, a dorsal somatosensory-motor network, and a default mode network. Disruptions to the gut-brain axis, which sustains interoceptive feedback between the central nervous system and the viscera, are thought to be involved in various disorders; manifestation of the infra-slow rhythm of the stomach in brain rsfMRI data could be useful for studies in clinical populations.

Familial Obesity Risk and Current Excess Weight Influence Brain Structure in Adolescents.

OBJECTIVE: Obesity risk transmits from parents to children. Underlying neural mechanisms were investigated in this study by evaluating influences of familial obesity risk defined by maternal obesity and influences of current overweight on three indices of brain structure in adolescents. METHODS: In total, 22 lean adolescents with lean mothers (lean low-risk), 25 lean adolescents with mothers with obesity/overweight (lean high-risk), and 36 adolescents with obesity/overweight underwent structural MRI scans for estimation of regional gray and white matter volume and cortical thickness. RESULTS: The lean high-risk compared with the lean low-risk group demonstrated lower gray and white matter volume and cortical thickness in the postcentral gyrus (somatosensory cortex), lower gray and white matter volume in the opercular cortex (taste cortex), lower gray matter volume and cortical thickness in the anterior cingulate cortex, and lower cortical thickness in the precuneus. Comparisons of the lean and obesity/overweight groups revealed further structural alterations in the postcentral gyrus, posterior cingulate gyrus, and middle temporal gyrus. CONCLUSIONS: Familial obesity risk and current obesity/overweight were associated with overlapping and distinct patterns of brain structure alterations. Longitudinal studies are warranted to investigate whether structural changes associated with familial obesity risk predict future weight trajectories.

Predicted DRD4 prefrontal gene expression moderates snack intake and stress perception in response to the environment in adolescents.

Body weight is substantially determined by eating behaviors, which are themselves driven by biological factors interacting with the environment. Previous studies in young children suggest that genetic influences on dopamine function may confer differential susceptibility to the environment in such a way that increases behavioral obesity risk in a lower socioeconomic status (SES) environment but decreases it in a higher SES environment. We aimed to test if this pattern of effect could also be observed in adolescence, another critical period for development in brain and behavior, using a novel measure of predicted expression of the dopamine receptor 4 (DRD4) gene in prefrontal cortex. In a sample of 76 adolescents (37 boys and 39 girls from Baltimore, Maryland/US, aged 14-18y), we estimated individual levels of DRD4 gene expression (PredDRD4) in prefrontal cortex from individual genomic data using PrediXcan, and tested interactions with a composite SES score derived from their annual household income, maternal education, food insecurity, perceived resource availability, and receipt of public assistance. Primary outcomes were snack intake during a multi-item ad libitum meal test, and food-related impulsivity assessed using a food-adapted go/no-go task. A linear regression model adjusted for sex, BMI z-score, and genetic ethnicity demonstrated a PredDRD4 by composite SES score interaction for snack intake (p = 0.009), such that adolescents who had lower PredDRD4 levels exhibited greater snack intake in the lower SES group, but lesser snack intake in the higher SES group. Exploratory analysis revealed a similar pattern for scores on the Perceived Stress Scale (p = 0.001) such that the low PredDRD4 group reported higher stress in the lower SES group, but less stress in the higher SES group, suggesting that PredDRD4 may act in part by affecting perceptions of the environment. These results are consistent with a differential susceptibility model in which genes influencing environmental responsiveness interact with environments varying in obesogenicity to confer behavioral obesity risk in a less favorable environment, but behavioral obesity protection in a favorable one.

Taste-related reward is associated with weight loss following bariatric surgery.

BACKGROUNDBariatric surgeries are the most effective treatments for successful and sustained weight loss, but individuals vary in treatment response. Understanding the neurobiological and behavioral mechanisms accounting for this variation could lead to the development of personalized therapeutic approaches and improve treatment outcomes. The primary objectives of this study were to investigate changes in taste preferences and taste-induced brain responses after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) and to identify potential taste-related predictors of weight loss.METHODSFemales, ages 18 to 55, with a body mass index greater than or equal to 35 kg/m2, and approved for bariatric surgery at the Johns Hopkins Center for Bariatric Surgery were recruited for participation. Demographics, anthropometrics, liking ratings, and neural responses to varying concentrations of sucrose plus fat mixtures were assessed before and after surgery via visual analog scales and functional MRI.RESULTSBariatric surgery produced decreases in liking for sucrose-sweetened mixtures. Greater preference for sucrose-sweetened mixtures before surgery was associated with greater weight loss in RYGB, but not VSG. In the RYGB group only, individuals who showed lower taste-induced activation in the ventral tegmental area (VTA) before surgery and greater changes in taste-induced VTA activation 2 weeks following surgery experienced increased weight loss.CONCLUSIONThe anatomical and/or metabolic changes associated with RYGB may more effectively "reset" the neural processing of reward stimuli, thereby rescuing the blunted activation in the mesolimbic pathway found in patients with obesity. Further, these findings suggest that RYGB may be particularly effective in patients with a preference for sweet foods.FUNDINGNIH K23DK100559 and Dalio Philanthropies.

Short-term improvements in cognitive function following vertical sleeve gastrectomy and Roux-en Y gastric bypass: a direct comparison study.

BACKGROUND: Cognitive deficits are observed in individuals with obesity. While bariatric surgery can reverse these deficits, it remains unclear whether surgery type differentially influences cognitive outcome. We compared the extent to which vertical sleeve gastrectomy (VSG) and Roux-en Y gastric bypass (RYGB) ameliorated cognitive impairments associated with obesity. METHODS: Female participants approved for VSG (N = 18) or RYGB (N = 18) were administered cognitive measures spanning the domains of attention [Hopkins Verbal Learning Test (HVLT) Trial 1 and Letter Number Sequencing], processing speed [Stroop Color Trial, Symbol Digit Modalities Test, and Trail Making Part A], memory [HVLT Retained and HVLT Discrimination Index], and executive functioning (Stroop Color Word Trials and Trail Making Part B-A) prior to surgery and at 2 weeks and 3 months following surgery. Scores for each cognitive domain were calculated and compared between surgical cohorts using repeated measures analyses of variance. RESULTS: Significant weight loss was observed 2 weeks and 3 months following RYGB and VSG and was accompanied by improvements in processing speed and executive functioning. Patients who received RYGB also experienced improved attention as early as 2 weeks, which persisted at 3 months. This was not observed in individuals who underwent VSG. No changes in memory were observed from baseline measures in either group. CONCLUSIONS: This is the first report of cognitive improvements following VSG and the first direct comparison of cognitive improvements following RYGB and VSG. Short-term improvements in specific domains of cognitive function are observed at the beginning of the active weight loss phase following bariatric surgery that persisted to 3 months. The anatomical distinction between the two surgeries and resulting differential metabolic profiles may be responsible for the improvements in attention observed following RYGB but not following VSG.

Does taste preference predict weight regain after bariatric surgery?

BACKGROUND: While bariatric surgery is well established as a means of inducing sustained weight loss, the rate of weight loss typically declines after a year, and weight regain has been observed. Preoperative taste preferences have been suspected to play a role in weight regain, possibly by influencing post-operative dietary practices. We sought to investigate the association between preoperative taste preferences and weight regain following bariatric surgery. METHODS: Patients who underwent bariatric surgery with at least 2 years of follow-up were included. Demographics and weight were collected in follow-up visits; while patient recall of preoperative taste preference was assessed, using a multiple-choice question in the study survey administered at least 6 months post-surgery. Weight regain was calculated as weight at 2 years minus weight at 1 year post-surgery, with weight regain denoted by positive values and weight loss by negative. Linear regression models were utilized to study associations between weight regain and preoperative taste preferences with and without adjusting for demographic factors and surgery type. RESULTS: Patients undergoing RYGB had less weight regain (- 4.5 kg, p = 0.033) compared to patients undergoing VSG. Compared to patients with no preferences, patients with sweet food or salty food preferences had 5.5 kg (p = 0.038) and 6.1 kg (p = 0.048) weight regain, respectively, at 2 years post-surgery. After adjustment, patients with salty food preference had 6.8 kg (p = 0.027) weight regain compared to patients with no preferences. CONCLUSIONS: Preoperative salty taste preference was associated with weight regain at 2 years post-surgery in patients undergoing bariatric surgery. Findings of this project might have implications for predicting long-term weight loss maintenance for patients with known preoperative taste preferences. Our study suggests that patients with preoperative salty taste preference may need further post-operative psychosocial support and resources to prevent weight regain and to ensure healthy and sufficient weight loss.

Detection of maltodextrin and its discrimination from sucrose are independent of the T1R2 + T1R3 heterodimer.

Maltodextrins, such as Maltrin and Polycose, are glucose polymer mixtures of varying chain lengths that are palatable to rodents. Although glucose and other sugars activate the T1R2 + T1R3 "sweet" taste receptor, recent evidence from T1R2- or T1R3-knockout (KO) mice suggests that maltodextrins, despite their glucose polymer composition, activate a separate receptor mechanism to generate a taste percept qualitatively distinguishable from that of sweeteners. However, explicit discrimination of maltodextrins from prototypical sweeteners has not yet been psychophysically tested in any murine model. Therefore, mice lacking T1R2 + T1R3 and wild-type controls were tested in a two-response taste discrimination task to determine whether maltodextrins are 1) detectable when both receptor subunits are absent and 2) perceptually distinct from that of sucrose irrespective of viscosity, intensity, and hedonics. Most KO mice displayed similar Polycose sensitivity as controls. However, some KO mice were only sensitive to the higher Polycose concentrations, implicating potential allelic variation in the putative polysaccharide receptor or downstream pathways unmasked by the absence of T1R2 + T1R3. Varied Maltrin and sucrose concentrations of approximately matched viscosities were then presented to render the oral somatosensory features, intensity, and hedonic value of the solutions irrelevant. Although both genotypes competently discriminated Maltrin from sucrose, performance was apparently driven by the different orosensory percepts of the two stimuli in control mice and the presence of a Maltrin but not sucrose orosensory cue in KO mice. These data support the proposed presence of an orosensory receptor mechanism that gives rise to a qualitatively distinguishable sensation from that of sucrose.

The importance of the presence of a 5'-ribonucleotide and the contribution of the T1R1 + T1R3 heterodimer and an additional low-affinity receptor in the taste detection of L-glutamate as assessed psychophysically.

The molecular receptors underlying the purported "umami" taste quality commonly associated with l-glutamate have been controversial. Evidence supports the involvement of the T1R1 + T1R3 heterodimer, a GPCR broadly tuned to l-amino acids, but variants of two mGluRs expressed in taste buds have also been implicated. Using a rigorous psychophysical taste-testing paradigm, we demonstrated impaired, if not eliminated, detection of MSG in WT and T1R1, T1R2, T1R3, and T1R2 + T1R3 KO mice when the contribution of sodium was minimized by the epithelial sodium channel blocker amiloride. When inosine 5'-monophosphate (IMP), a ribonucleotide that potentiates the l-glutamate signal through the T1R1 + T1R3 heterodimer, was added, the WT and T1R2 KO mice were able to detect the compound stimulus across all MSG (+amiloride) concentrations due, in part, to the taste of IMP. In contrast, mice lacking T1R1 or T1R3 could not detect IMP alone, yet some were able to detect MSG + amiloride + IMP, but only at the higher MSG concentrations. Interestingly, the sensitivity of T1R1 KO mice to another l-amino acid, lysine, was unimpaired, suggesting that some l-amino acids can be detected through T1R1 + T1R3-independent receptors without sensitivity loss. Given that IMP is not thought to affect mGluRs, behavioral detection of l-glutamate appears to require the contribution of the T1R1 + T1R3 receptor. However, the partial competence observed in some T1R1 and T1R3 KO mice when MSG + amiloride + IMP was tested suggests that a T1R1 or T1R3 homodimer or an unidentified protein, perhaps in conjunction with T1R1 or T1R3, can serve as a low-affinity taste receptor for l-glutamate in the presence of IMP.

Contribution of the TRPV1 channel to salt taste quality in mice as assessed by conditioned taste aversion generalization and chorda tympani nerve responses.

In rodents, at least two transduction mechanisms are involved in salt taste: 1) the sodium-selective epithelial sodium channel, blocked by topical amiloride administration, and 2) one or more amiloride-insensitive cation-nonselective pathways. Whereas electrophysiological evidence from the chorda tympani nerve (CT) has implicated the transient receptor potential vanilloid-1 (TRPV1) channel as a major component of amiloride-insensitive salt taste transduction, behavioral results have provided only equivocal support. Using a brief-access taste test, we examined generalization profiles of water-deprived C57BL/6J (WT) and TRPV1 knockout (KO) mice conditioned (via LiCl injection) to avoid 100 µM amiloride-prepared 0.25 M NaCl and tested with 0.25 M NaCl, sodium gluconate, KCl, NH(4)Cl, 6.625 mM citric acid, 0.15 mM quinine, and 0.5 M sucrose. Both LiCl-injected WT and TRPV1 KO groups learned to avoid NaCl+amiloride relative to controls, but their generalization profiles did not differ; LiCl-injected mice avoided the nonsodium salts and quinine suggesting that a TRPV1-independent pathway contributes to the taste quality of the amiloride-insensitive portion of the NaCl signal. Repeating the experiment but doubling all stimulus concentrations revealed a difference in generalization profiles between genotypes. While both LiCl-injected groups avoided the nonsodium salts and quinine, only WT mice avoided the sodium salts and citric acid. CT responses to these stimuli and a concentration series of NaCl and KCl with and without amiloride did not differ between genotypes. Thus, in our study, TRPV1 did not appear to contribute to sodium salt perception based on gustatory signals, at least in the CT, but may have contributed to the oral somatosensory features of sodium.

Behavioral evidence for a glucose polymer taste receptor that is independent of the T1R2+3 heterodimer in a mouse model.

Although it is clear that the heterodimer formed by the T1R2 and T1R3 proteins serves as the primary taste receptor for sweeteners, there is growing evidence that responses to glucose polymers may be mediated by a different taste receptor. Here we report that although T1R2 knock-out (KO) and T1R3 KO mice displayed severely impaired responding to glucose, maltose, and maltotriose in an initial session of a brief-access taste test (5 s trials, 25 min sessions) relative to wild-type (WT) mice, they subsequently increased their licking as a function of concentration for maltose and maltotriose with continued testing, presumably due to associating weak oral cues with positive post-ingestive consequences. Interestingly, these KO mice displayed relatively normal concentration-dependent licking to Polycose, a mixture of glucose polymers, even in the first session. Importantly, the experience-dependent increase in responsiveness to the sugars observed with the T1R2 and T1R3 single KO mice was not statistically significant in the T1R2/3 double KO mice. The double KO mice, however, still displayed significant concentration-dependent responding to Polycose in the first test session, albeit lick rates were slightly lower than those seen for WT mice, perhaps because small amounts of glucose, maltose, and maltotriose found in Polycose were enhancing the signal in WT mice or because T1R2 or T1R3 can possibly heteromerize with another protein to form a fully functional glucose polymer receptor. These findings provide behavioral evidence that glucose polymers, with an optimal chain length greater than three glucose moieties, stimulate a taste receptor independent of the T1R2+3 heterodimer.

Can clinical prediction rules used in acute pediatric ankle and midfoot injuries be applied to an adult population?

BACKGROUND: Almost every patient who comes to an emergency department (ED) with the chief complaint of ankle or foot pain will receive a radiograph, but less than 15% will have a finding positive for ankle or midfoot fracture. In an effort to reduce the number of radiographs performed, clinicians have attempted to derive a set of maximally sensitive clinical prediction rules. Dayan et al (Acad Emerg Med. 2004;11(7):736-745) in 2004 derived a set of such rules for children. These rules have not yet been evaluated in the adult population. OBJECTIVE: The objective of this study is to apply the existing clinical prediction rules used to identify children with fractures after twisting injuries of the ankle to a population that includes adults. METHODS: This was a prospective observational study using convenience sampling. Patients older than 2 years presenting to the ED or associated urgent care center with the chief complaint of an ankle or foot injury were considered eligible for enrollment into the study. After informed consent was obtained, 11 physical examination variables were assessed. Radiographs were obtained and reported, and the radiograph results were noted on the patient's data sheet. Based on the radiograph results, sensitivity and specificity of each of the physical examination variables were analyzed. RESULTS: Sixty-eight patients were eligible, and 29 patients were enrolled after exclusion criteria were applied (median age, 34 years). Three patients were diagnosed with a malleolar zone fracture, and 2 patients were diagnosed with a midfoot zone fracture. Five indicators were found to be 100% sensitive for ankle fracture, and 2 indicators were 100% sensitive for midfoot fracture. CONCLUSIONS: The same indicators found to be predictive of high risk for fracture in a population of pediatric patients were found to be predictive in a population including adults.

The functional role of the T1R family of receptors in sweet taste and feeding.

The discovery of the T1R family of Class C G protein-coupled receptors in the peripheral gustatory system a decade ago has been a tremendous advance for taste research, and its conceptual reach has extended to other organ systems. There are three proteins in the family, T1R1, T1R2, and T1R3, encoded by their respective genes, Tas1r1, Tas1r2, and Tas1r3. T1R2 combines with T1R3 to form a heterodimer that binds with sugars and other sweeteners. T1R3 also combines with T1R1 to form a heterodimer that binds with l-amino acids. These proteins are expressed not only in taste bud cells, but one or more of these T1Rs have also been identified in the nasal epithelium, gut, pancreas, liver, kidney, testes and brain in various mammalian species. Here we review current perspectives regarding the functional role of these receptors, concentrating on sweet taste and feeding. We also discuss behavioral findings suggesting that a glucose polymer mixture, Polycose, which rodents avidly prefer, appears to activate a receptor that does not depend on the combined expression of T1R2 and T1R3. In addition, although the T1Rs have been implicated as playing a role in glucose sensing, T1R2 knock-out (KO) and T1R3 KO mice display normal chow and fluid intake as well as normal body weight compared with same-sex littermate wild type (WT) controls. Moreover, regardless of whether they are fasted or not, these KO mice do not differ from their WT counterparts in their Polycose intake across a broad range of concentrations in 30-minute intake tests. The functional implications of these results and those in the literature are considered.